Human receptor for activated protein kinase C1 associates with polyglutamine aggregates and modulates polyglutamine toxicity.
Formation of SDS-insoluble protein aggregates in affected neurons is a cellular pathological feature of polyglutamine (polyQ) disease. We identified a multi-WD-domain protein, receptor for activated protein kinase C1 (RACK1), as a novel polyQ aggregate component from a Drosophila transgenic polyQ disease model. We showed that WD domains were crucial determinants for the recruitment of RACK1 to polyQ aggregates. Over-expression of the human RACK1 protein suppressed polyQ-induced neurodegeneration in vivo. This is the first report to demonstrate the involvement of WD-domain proteins in polyQ pathogenesis, and the proteomic approach described here can be applied to the investigation of other protein aggregation disorders including Alzheimer's and Parkinson's diseases.
Lam
Wun
W
Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Chan
Wing Man
WM
Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Lo
Tsz Wai
TW
Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Wong
Azaria Kam Yan
AKY
Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Wu
Chi Chung
CC
Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Chan
Ho Yin Edwin
HYE
Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Department of Biochemistry (Science), The Chinese University of Hong Kong, Laboratory of Drosophila Research, Molecular Biotechnology Programme, Room 509B, Mong Man Wai Building, Shatin, N.T., Hong Kong SAR, China. Electronic address: hyechan@cuhk.edu.hk.
D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D005561:Formates / Q000737:chemistry; D019204:GTP-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D020271:Heredodegenerative Disorders, Nervous System / Q000201:enzymology / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D017434:Protein Structure, Tertiary; D040901:Proteomics; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D005561:Formates; D009363:Neoplasm Proteins; D010455:Peptides; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C030544:formic acid; C097188:polyglutamine; D019204:GTP-Binding Proteins